Monocyte Chemoattractant Protein-1 Levels Research Articles

TUBULAR BIOMARKERS IN PROTEINURIC KIDNEY DISEASE: Histology correlation and kidney prognosis of tubular biomarkers

Abstract Background Proteinuria is not only a biomarker of chronic kidney disease (CKD) but also a driver of CKD progression. The aim of this study was to evaluate serum and urinary tubular biomarkers in patients with biopsied proteinuric kidney disease and to correlate them with histology and kidney outcomes. Methods A single-center retrospective study was conducted on a cohort of 156 patients from January 2016 to December 2021. The following urinary and serum biomarkers were analyzed on the day of kidney biopsy: β2-mcg (beta 2 microglobulin), α1-mcg (alpha 1 microglobulin), NGAL (neutrophil gelatinase-associated lipocalin), uKIM-1 (kidney injury molecule-1), MCP-1 (monocyte chemoattractant protein-1), uDKK-3 (urinary dickkopf-3), uUMOD (uromodulin), sKIM-1 and sUMOD. A composite outcome of kidney progression or death was recorded during a median follow-up period of 26 months. Results Multivariate regression analysis identified sUMOD (beta -0.357, p<0.001) and uDKK3 (beta 0.483, p<0.001) as independent predictors of interstitial fibrosis, adjusted for age, eGFR and log proteinuria. Elevated levels of MCP-1 [OR=15.61, 95% CI (3.52-69.20)] were associated with a higher risk of cortical interstitial inflammation >10% adjusted for eGFR, log proteinuria and microhematuria. Upper tertiles of uDKK3 were associated with greater eGFR decline during follow-up. Although not a predictor of the composite outcome, doubling of uDKK3 was a predictor of kidney events (HR 2.26, 95% CI 1.04-4.94) after adjustment for interstitial fibrosis, eGFR, and proteinuria. Conclusions Tubular markers may have prognostic value in proteinuric kidney disease, correlating with specific histologic parameters and identifying cases at higher risk of CKD progression.

Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive loss of motor neurons. Emerging evidence suggests a potential link between metabolic dysregulation and ALS pathogenesis. This study aimed to investigate the relationship between metabolic hormones and disease progression in ALS patients. A cross-sectional study was conducted involving 44 ALS patients recruited from a tertiary care center. Serum levels of insulin, total amylin, C-peptide, active ghrelin, GIP (gastric inhibitory peptide), GLP-1 active (glucagon-like peptide-1), glucagon, PYY (peptide YY), PP (pancreatic polypeptide), leptin, interleukin-6, MCP-1 (monocyte chemoattractant protein-1), and TNFα (tumor necrosis factor alpha) were measured, and correlations with ALSFRS-R, evolution scores, and biomarkers were analyzed using Spearman correlation coefficients. Subgroup analyses based on ALS subtypes, progression pattern of disease, and disease progression rate patterns were performed. Significant correlations were observed between metabolic hormones and ALS evolution scores. Insulin and amylin exhibited strong correlations with disease progression and clinical functional outcomes, with insulin showing particularly robust associations. Other hormones such as C-peptide, leptin, and GLP-1 also showed correlations with ALS progression and functional status. Subgroup analyses revealed differences in hormone levels based on sex and disease evolution patterns, with male patients showing higher amylin and glucagon levels. ALS patients with slower disease progression exhibited elevated levels of amylin and insulin. Our findings suggest a potential role for metabolic hormones in modulating ALS progression and functional outcomes. Further research is needed to elucidate the underlying mechanisms and explore the therapeutic implications of targeting metabolic pathways in ALS management.

Podocyte-Specific Deletion of MCP-1 Fails to Protect against Angiotensin II- or Adriamycin-Induced Glomerular Disease.

Investigating the role of podocytes in proteinuric disease is imperative to address the increasing global burden of chronic kidney disease (CKD). Studies strongly implicate increased levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in proteinuric CKD. Since podocytes express the receptor for MCP-1 (i.e., CCR2), we hypothesized that podocyte-specific MCP-1 production in response to stimuli could activate its receptor in an autocrine manner, leading to further podocyte injury. To test this hypothesis, we generated podocyte-specific MCP-1 knockout mice (Podo-Mcp-1fl/fl) and exposed them to proteinuric injury induced by either angiotensin II (Ang II; 1.5 mg/kg/d, osmotic minipump) or Adriamycin (Adr; 18 mg/kg, intravenous bolus). At baseline, there were no between-group differences in body weight, histology, albuminuria, and podocyte markers. After 28 days, there were no between-group differences in survival, change in body weight, albuminuria, kidney function, glomerular injury, and tubulointerstitial fibrosis. The lack of protection in the knockout mice suggests that podocyte-specific MCP-1 production is not a major contributor to either Ang II- or Adr-induced glomerular disease, implicating that another cell type is the source of pathogenic MCP-1 production in CKD.

Plasma IGFBP-3 and IGFBP-5 levels are decreased during acute manic episodes in bipolar disorder patients.

Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1β (MIP-1β). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1β levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.

Alleviating iatrogenic effects of paclitaxel via antiinflammatory treatment.

Paclitaxel (PTX) is touted as an essential medicine due to its extensive use as a chemotherapeutic agent for various cancers and an antiproliferative agent for endovascular applications. Emerging studies in cardio-oncology implicate various vascular complications of chemotherapeutic agents. We evaluated the inflammatory response induced by the systemic administration of PTX. The investigation included RNAseq analysis of primary human endothelial cells (ECs) treated with PTX to identify transcriptional changes in pro-inflammatory mediators. Additionally, we used dexamethasone (DEX), a well-known antiinflammatory compound, to assess its effectiveness in counteracting these PTX-induced changes. Further, we studied the effects of PTX on monocyte chemoattractant protein-1 (MCP-1) levels in the media of ECs. The study also extended to in vivo analysis, where a group of mice was injected with PTX and subsequently harvested at different times to assess the immediate and delayed effects of PTX on inflammatory mediators in blood and aortic ECs. Our RNAseq analysis revealed that PTX treatment led to significant transcriptional perturbations in pro-inflammatory mediators such as MCP-1 and CD137 within primary human ECs. These changes were effectively abrogated when DEX was administered. In vitro experiments showed a marked increase in MCP-1 levels in EC media following PTX treatment, which returned to baseline upon treatment with DEX. In vivo, we observed a threefold increase in MCP-1 levels in blood and aortic ECs 12 h post-PTX administration. Similar trends were noted for CD137 and other downstream mediators like tissue factor, vascular cell adhesion molecule 1, and E-selectin in aortic ECs. Our findings illustrate that PTX exposure induces an upregulation of atherothrombotic mediators, which can be alleviated with concurrent administration of DEX. Considering these observations, further long-term investigations should focus on understanding the systemic implications associated with PTX-based therapies and explore the clinical relevance of DEX in mitigating such risks.

No side effects on rabbit retina or vitreous microenvironment by nd:YAG laser vitreolysis.

To explore the safety of Neodymium:Yttrium-aluminum-garnet (Nd:YAG) laser vitreolysis based on the histological examination of the retina and the alteration of vitreous cytokines in the rabbits. Nine male New Zealand rabbits underwent Nd:YAG laser vitreolysis of 10mJ x 500 pulses in the left eyes, while the right eyes were used as controls. Intraocular pressure, color fundus photography, and ultrasound B scan were measured before, as well as 1day, 4 weeks, and 12 weeks after Nd:YAG laser vitreolysis. Three rabbits were euthanized 1day, 4 weeks, and 12 weeks after treatment, respectively. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and hematoxylin-eosin (H&E) staining were used to look for pathological changes in the retina. An enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of vascular endothelial growth factor (VEGF) and some inflammatory cytokines, including interferon inducible protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1) and interlenkin 6 (IL-6) in the vitreous humor. The ascorbic acid (AsA) and total reactive antioxidant potential (TRAP) in the vitreous humor were also measured. Following Nd:YAG laser vitreolysis, the levels of VEGF, IP-10, MCP-1, IL6, AsA, and TRAP in the vitreous humor did not change substantially (P > 0.05). There were no detectable pathological changes in the retinal tissues, and no apoptotic signal was found. Rabbits tolerate Nd:YAG laser vitreolysis without observable impact on retinal tissue or the microenvironment of the vitreous.

Transgenic human C-reactive protein affects oxidative stress but not inflammation biomarkers in the aorta of spontaneously hypertensive rats

BackgroundC-reactive protein (CRP) is an acute inflammatory protein detected in obese patients with metabolic syndrome. Moreover, increased CRP levels have been linked with atherosclerotic disease, congestive heart failure, and ischemic heart disease, suggesting that it is not only a biomarker but also plays an active role in the pathophysiology of cardiovascular diseases. Since endothelial dysfunction plays an essential role in various cardiovascular pathologies and is characterized by increased expression of cell adhesion molecules and inflammatory markers, we aimed to detect specific markers of endothelial dysfunction, inflammation, and oxidative stress in spontaneously hypertensive rats (SHR) expressing human CRP. This model is genetically predisposed to the development of the metabolic syndrome.MethodsTransgenic SHR male rats (SHR-CRP) and non-transgenic SHR (SHR) at the age of 8 months were used. Metabolic profile (including serum and tissue triglyceride (TAG), serum insulin concentrations, insulin-stimulated incorporation of glucose, and serum non-esterified fatty acids (NEFA) levels) was measured. In addition, human serum CRP, MCP-1 (monocyte chemoattractant protein-1), and adiponectin were evaluated by means of ELISA, histological analysis was used to study morphological changes in the aorta, and western blot analysis of aortic tissue was performed to detect expression of endothelial, inflammatory, and oxidative stress markers.ResultsThe presence of human CRP was associated with significantly decreased insulin-stimulated glycogenesis in skeletal muscle, increased muscle and hepatic accumulation of TAG and decreased plasmatic cGMP concentrations, reduced adiponectin levels, and increased monocyte chemoattractant protein-1 (MCP-1) levels in the blood, suggesting pro-inflammatory and presence of multiple features of metabolic syndrome in SHR-CRP animals. Histological analysis of aortic sections did not reveal any visible morphological changes in animals from both SHR and SHR-CRP rats. Western blot analysis of the expression of proteins related to the proper function of endothelium demonstrated significant differences in the expression of p-eNOS/eNOS in the aorta, although endoglin (ENG) protein expression remained unaffected. In addition, the presence of human CRP in SHR in this study did not affect the expression of inflammatory markers, namely p-NFkB, P-selectin, and COX2 in the aorta. On the other hand, biomarkers related to oxidative stress, such as HO-1 and SOD3, were significantly changed, indicating the induction of oxidative stress.ConclusionsOur findings demonstrate that CRP alone cannot fully induce the expression of endothelial dysfunction biomarkers, suggesting other risk factors of cardiovascular disorders are necessary to be involved to induce endothelial dysfunction with CRP.

Protective effect of modified Huangqi Chifeng decoction on immunoglobulin A nephropathy through toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway.

To examine the nephroprotective mechanism of modified Huangqi Chifeng decoction (, MHCD) in immunoglobulin A nephropathy (IgAN) rats. To establish the IgAN rat model, the bovine serum albumin, lipopolysaccharide, and carbon tetrachloride 4 method was employed. The rats were then randomly assigned to the control, model, telmisartan, and high-, medium-, and low-dose MHCD groups, and were administered the respective treatments via intragastric administration for 8 weeks. The levels of 24-h urinary protein, serum creatinine (CRE), and blood urea nitrogen (BUN) were measured in each group. Pathological alterations were detected. IgA deposition was visualized through the use of immunofluorescence staining. The ultrastructure of the kidney was observed using a transmission electron microscope. The expression levels of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and transforming growth factor-β1 (TGF-β1) were examined by immunohistochemistry and quantitative polymerase chain reaction. Levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB) P65, were examined by immunohistochemistry, Western blotting, and quantitative polymerase chain reaction. The 24-h urine protein level in each group increased significantly at week 6, and worsen from then on. But this process can be reversed by treatments of telmisartan, and high-, medium-, and low-dose of MHCD, and these treatments did not affect renal function. Telmisartan, and high-, and medium-dose of MHCD reduced IgA deposition. Renal histopathology demonstrated the protective effect of high-, medium-, and low-dose of MHCD against kidney injury. The expression levels of MCP-1, IL-6, and TGF-β1 in kidney tissues were downregulated by low, medium and high doses of MHCD treatment. Additionally, treatment of low, medium and high doses of MHCD decreased the protein and mRNA levels of TLR4, MyD88, and NF-κB. MHCD exerted nephroprotective effects on IgAN rats, and MHCD regulated the expressions of key targets in TLR4/MyD88/NF-κB signaling pathway, thereby alleviating renal inflammation by inhibiting MCP-1, IL-6 expressions, and ameliorating renal fibrosis by inhibiting TGF-β1 expression.

Plasma and peritoneal fluid cytokine profiles in patient with Essure® implant: Towards a molecular signature?

Objective(s)Many patients with Essure® implant may experience adverse events related to the device. Although local inflammation does not appear to be the pathophysiological mechanism underlying the symptoms, systemic inflammation could play a role. In the present study, as cytokines are involved in the inflammatory process, we proposed to investigate the profile of circulating and peritoneal cytokines. Study designIn this retrospective study, we evaluated the levels of cytokines in peritoneal fluid (PF) as well as in plasma sample from three different groups: Essure® group, endometriosis group (known to be associated with immune dysregulation), and control group. ResultsThere were 60 symptomatic patients with Essure® device, 30 patients with endometriosis and a control group of 30 patients. The PF levels of Interleukin-10 (IL-10), Interleukin-6 (IL-6), and Monocyte chemoattractant protein-1 (MCP-1) were statistically higher in endometriosis group than in Essure® group and control group. The plasma level of MCP-1 was higher in Essure® group than in endometriosis group and control group. The plasma level of TNF-α was higher in Essure® group than in control group. ConclusionsThe chemokine MCP-1 as well as the pro-inflammatory TNF-α, are known to be increased in patients with fibromyalgia and chronic fatigue syndrome. Since patients with Essure® may exhibit symptoms similar to fibromyalgia, MCP-1 and TNF-α may be relevant markers in symptomatic patients with Essure®. Because of the lack of longitudinal data (no evaluation of postoperative cytokine profile and no assessment of the level of clinical improvement), other studies are needed to confirm these preliminary results.

Abstract 7304: Modulation of cytokine and chemokine profiles in pancreatic tumors and plasma via stage-specific intervention with Momordica Charantia juice in the LSL-KrasG12D/+, p48Cre/+ mouse model

Abstract According to the American Cancer Society ≈64,050 people will be newly diagnosed with pancreatic cancer in the United States, while ≈55, 550 (men and women numbers combined) will die of this malignancy in 2023 alone. Epidemiological studies have indicated that a diet rich in natural agents might reduce pancreatic ductal adenocarcinoma (PDAC) risk, prompting investigations into a natural agent with health benefits in pancreatic diseases [such as the fruits of Momordica Charantia (Bitter Melon)] as a potential natural and non-toxic anti-cancer approach against PDAC. Previously we have reported the protective effects of oral Bitter Melon Juice (BMJ-standardized-lyophilized powder) against growth and progression of PDAC in preclinical animal models (xenograft and patient-derived tumor models). In a recent study we reported the efficacy of BMJ against pancreatic cancer in the LSL-KrasG12D/+, p48Cre/+ transgenic mouse model [this model mimics the stage-specific progression of intraepithelial neoplasms to PDAC as it occurs in humans]. Both male and female LSL-KrasG12D/+, p48Cre/+ transgenic mice were subjected to BMJ intervention (daily oral gavage, dose: 200mg/kg body wt.) during different stages in disease progression. Intervention was started at 4 or 15 weeks of mice age and continued till study end (10 and 30 weeks of mice age respectively). Additionally, in one group of mice, intervention was initiated at 6 weeks of mice age and continued till 41 weeks of mice age (study end). Outcomes were compared with wild-type and disease-positive untreated control groups. Pancreatic tissue/tumors were harvested at study end and blood plasma was also collected. In the present study, we performed a stage specific evaluation of tissue and plasma cytokine/chemokine profiling after BMJ intervention to gain detailed mechanistic insights into the potential of BMJ to mediate it is anti-pancreatic cancer effect via modulation of inflammatory pathways associated with PDAC growth and progression. BMJ (15 weeks of treatment) demonstrated a significant response in modulating cytokine/chemokine profiles in LSL KrasG12D/+, p48Cre/+ mice pancreatic cancerous tissues (30 weeks old mice). BMJ intervention specifically downregulated the levels of monocyte chemoattractant protein (MCP-1), macrophage inflammatory protein-1 (MIP-1-gamma), tumor necrosis factor (TNF) receptor (TNFR1), Vascular cell adhesion molecule 1 (VCAM-1/CD106) and L-selectin (CD62L). Furthermore, Ingenuity Pathway Analysis indicated significant inhibitory predictions on TNF-α, NF-κB and MCP-1 (CCL-2) associated inflammatory pathways. Overall, these outcomes signify that the anti- cancer effects of BMJ in KRAS harboring PDAC tumors is associated with down-regulation of inflammatory pathways associated with growth and progression of pancreatic cancer. Citation Format: Lakshmi Sai Pratyusha Bugata, Robin Kumar, Md. Imtiazul Kabir, Rama Kant, Chapla Agarwal, Rajesh Agarwal, Komal Raina. Modulation of cytokine and chemokine profiles in pancreatic tumors and plasma via stage-specific intervention with Momordica Charantia juice in the LSL-KrasG12D/+, p48Cre/+ mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7304.

Xiasangju alleviate metabolic syndrome by enhancing noradrenaline biosynthesis and activating brown adipose tissue.

Metabolic syndrome (MetS) is a clinical condition associated with multiple metabolic risk factors leading to type 2 diabetes mellitus and other metabolic diseases. Recent evidence suggests that modulating adipose tissue to adaptive thermogenesis may offer therapeutic potential for MetS. Xiasangju (XSJ) is a marketed drug and dietary supplement used for the treatment of metabolic disease with anti-inflammatory activity. This study investigated the therapeutic effects of XSJ and the underlying mechanisms affecting the activation of brown adipose tissue (BAT) in MetS. The results revealed that XSJ ameliorated MetS by enhancing glucose and lipid metabolism, leading to reduced body weight and abdominal circumference, decreased adipose tissue and liver index, and improved blood glucose tolerance. XSJ administration stimulated catecholamine biosynthesis, increasing noradrenaline (NA) levels and activating NA-mediated proteins in BAT. Thus, BAT enhanced thermogenesis and oxidative phosphorylation (OXPHOS). Moreover, XSJ induced changes in gut microbiota composition, with an increase in Oscillibacter abundance and a decrease in Bilophila, Candidatus Stoquefichus, Holdemania, Parasutterella and Rothia. XSJ upregulated the proteins associated with intestinal tight junctions corresponding with lower serum lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α) monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) levels to maintain NA signaling transport. In summary, XSJ may alleviate MetS by promoting thermogenesis in BAT to ultimately boost energy metabolism through increasing NA biosynthesis, strengthening intestinal barrier integrity and reducing low-grade inflammation. These findings suggest XSJ has potential as a natural therapeutic agent for the treatment of MetS.

Combination of urinary biomarkers and machine-learning models provided a higher predictive accuracy to predict long-term treatment outcomes of patients with interstitial cystitis/bladder pain syndrome.

To identify predictive factors for satisfactory treatment outcome of the patients with IC/BPS using urine biomarkers and machine-learning models. The IC/BPS patients were prospectively enrolled and provide urine samples. The targeted analytes included inflammatory cytokines, neurotrophins, and oxidative stress biomarkers. The patients with overall subjective symptom improvement of ≥ 50% were considered to have satisfactory results. Binary logistic regression, receiver-operating characteristic (ROC) curve, machine-learning decision tree, and random forest models were used to analyze urinary biomarkers to predict satisfactory results. Altogether, 57.4% of the 291 IC/BPS patients obtained satisfactory results. The patients with satisfactory results had lower levels of baseline urinary inflammatory cytokines and oxidative biomarkers than patients without satisfying results, including interleukin-6, monocyte chemoattractant protein-1 (MCP-1), C-X-C motif chemokine 10 (CXCL10), oxidative stress biomarkers 8-hydroxy-2'-deoxyguanosine (8-OHDG), 8-isoprostane, and total antioxidant capacity (TAC). Logistic regression and multivariable analysis revealed that lower levels of urinary CXCL10, MCP-1, 8-OHDG, and 8-isoprostane were independent factors. The ROC curve revealed that MCP-1 level had best area under curve (AUC: 0.797). In machine-learning decision tree model, combination of urinary C-C motif chemokine 5, 8-isoprostane, TAC, MCP-1, and 8-OHDG could predict satisfactory results (accuracy: 0.81). The random forest model revealed that urinary 8-isoprostance, MCP-1, and 8-OHDG levels had the most important influence on accuracy. Machine learning decision tree model provided a higher accuracy for predicting treatment outcome of patients with IC/BPS than logistic regression, and levels of 8-isoprostance, MCP-1, and 8-OHDG had the most important influence on accuracy.

How is inflammation biology truly associated with depression in patients with stable coronary heart disease?: Insights from the heart and Soul study

Depression is known to be associated with inflammation among patients with established coronary heart disease (CHD), but it is unclear whether this is due to individual depression symptoms or to the broader construct of depression. We addressed this gap by using moderated non-linear factor analysis (MNLFA) to determine the extent that inflammation is associated with latent depression and/or individual symptoms in this patient group. We evaluated 1,024 outpatients with stable CHD from the baseline cross-sectional data of the Heart and Soul Study. Depression was assessed using the 9-item Patient Health Questionnaire, while inflammation was evaluated via C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels. MNLFA is based on the concept of model parameter moderation with regard to individual characteristics. Using the MNLFA approach, we simultaneously tested for differences in (1) latent depression, (2) individual depression items, and (3) the factor loading of the item on latent depression as a function of inflammatory markers, with and without covariate adjustment. Higher TNF-α levels were associated with both higher levels of a latent depression factor and greater endorsement of an individual symptom (appetite changes). Increased CRP levels were significantly associated with greater appetite changes, lower concentration difficulty, and greater fatigue. Elevated IL-6 levels were only related to greater fatigue, while increased MCP-1 levels were linked to greater sleep disturbance. After adjusting for covariates, some associations became insignificant. Inflammatory markers were not consistent predictors of factor loadings. This study represents the initial step to discussing how inflammation biology is truly related to depression among patients with established CHD.

Interleukin-6 trans-signaling regulates monocyte chemoattractant protein-1 production in immune-mediated necrotizing myopathy.

Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofiber necrosis and regeneration, myophagocytosis, and a sparse inflammatory infiltrate. The monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that regulates monocyte/macrophage infiltration into injured tissues. The interleukin-6 (IL-6) signalling in the induction of MCP-1 expression has not been investigated in IMNM. MCP-1 expression in muscle specimens was assessed using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated using the Meso Scale Discovery electrochemiluminescence system. Flow cytometry, RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase reporter assays, and chromatin immunoprecipitation-qPCR were performed to explore the effects of IL-6 signalling on MCP-1 production in human myoblasts. MCP-1 was scattered and was positively expressed within myofibers and a few inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 expression significantly correlated with myonecrosis, myoregeneration, and inflammatory infiltration. Serum MCP-1, IL-6, and the soluble form of the IL-6 receptor (sIL-6R) were elevated in patients with IMNM compared with controls. Serological MCP-1 levels were significantly associated with serum IL-6 expression and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced MCP-1 expression via the signal transducer and activator of transcription 3 (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched in the MCP-1 promoter region and promoted the transcription. IL-6 trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting inflammation through regulation of MCP-1 expression in IMNM.

The importance of the enzyme Gamma-glutamyltransferase in the pathogenic cluster in type2 diabetic patient.

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity. Methods. Eighty-five type 2 diabetes, aged 40-70 years with a duration of diabetes less than 6 years without infections, epilepsy, chronic liver or cardiac diseases, without alcohol consumption (>20 g/day) were divided in two subgroups, those with normal and those with high abnormal GGT. Results. The diabetic patients with high GGT (n=31) had dysglycaemia, dyslipidemia, higher inflammatory markers (CRP, TNF-α, MCP-1) and endothelial dysfunction (high leptin and sICAM). sICAM, serum MCP-1 and TNF-α levels had significant correlations with GGT activity (r= 0.38, r=0.30 and 0.26 respectively, p<0.05). Conclusion. This study underlines that in non-alcoholic diabetic patients, with a duration of the metabolic disease less than 6 years, sICAM, serum MCP-1 and TNF-α might play an important role in dysmetabolism, and higher level for GGT represents the "red flag" for this condition.

Characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction.

To investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD). In this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed. The PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β2 (TGF-β2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-β2 level were independent risk factors for PCD. A thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-β2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-β2 level are independent risk factors for PCD.

Comparative Levels of Urinary Biomarkers of Renal Injury and Inflammation Among Patients With Diabetic Nephropathy With or Without Hyperuricemia.

The association between hyperuricemia and development of progressive chronic kidney disease has received increasing attention in recent years. Recent preclinical studies have shown that non-crystalline uric acid can induce renal-specific arteriolopathy, leading to renal injury and tubulointerstitial inflammation. We conducted a open-label cross-sectional study of 25 patients with chronic kidney disease stage III (estimated glomerular filtration rate [eGFR], 7.0 mg/dL) levels of serum uric acid. To determine the correlation between hyperuricemia on urinary protein levels and renal disease progression, we retrospectively compared urine protein and eGFR data between the 2 groups. Eleven patients with normal uric acid levels and 14 with hyperuricemia were enrolled. Urinary levels of both kidney injury molecule-1 (KIM-1) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in patients with hyperuricemia. Among the normouricemic White and African American (AA) subgroups, there was no difference in KIM-1 or MCP-1 levels, whereas KIM-1 levels were significantly higher among hyperuricemic AA patients with hyperuricemia. Urinary protein was significantly higher between Whites and AA patients with serum uric acid level >7.0 mg/dL as well as patients with urinary KIM-1 levels >1000 pg/mg Cr. A trend toward a more rapid decline in eGFR was noted among hyperuricemic AAs; however, this trend was not statistically significant. Patients with type 2 diabetic nephropathy and persistently elevated serum uric acid levels express higher levels of both KIM-1 and MCP-1 reflective of on-going renal injury and inflammation.

Evaluation of Chemokines and Cytokines as Biomarkers for Disease Severity in COVID-19-Infected Patients

Background: Alterations in cytokine and chemokine levels during SARS-CoV-2 infection may serve as indicators of disease severity. Objectives: This study aimed to evaluate the levels of plasma cytokines and chemokines in patients with COVID-19. Methods: The study included 120 COVID-19 patients, divided into severe, mild, and recovered categories (n = 40 for each group). Plasma levels of cytokines such as interleukin 8 (IL-8) and tumor necrosis factor α (TNF-α) were measured using ELISA, while chemokines like monocyte chemoattractant protein 1 (MCP-1) and programmed death protein 1 (PD-1) were quantified through qRT-PCR. Results: A higher incidence of positive biomarkers IL-8, TNF-α, MCP-1, and PD-1 was observed in the severe group compared to the mild and recovered groups. Notably, the expression levels of PD-1 and MCP-1 were significantly elevated in severely infected individuals relative to those in healthy subjects. A strong positive correlation was also noted between PD-1 and MCP-1 levels in cases of severe infection. Conclusions: The findings suggest that MCP-1, PD-1, TNF-α, and IL-8 could act as biomarkers for assessing the severity of COVID-19 infections. These results aim to deepen our understanding of the immunopathological mechanisms at play in this disease.

Exploring the relations of NLR, hsCRP and MCP-1 with type 2 diabetic kidney disease: a cross-sectional study

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil–lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060–20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026–1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577–0.863, P < 0.001) and 0.862 (95% CI 0.7787–0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

To study the association of pro-inflammatory markers with incident diabetes in India. We did a nested case-control study within the CARRS (Centre for ArdiometabolicRiskReduction inSouth Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI:1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI:1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI:0.06, 0.55]). Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.